Abstract
Self-renewal and differentiation of mammalian haematopoietic stem cells (HSCs) are controlled by a specialized microenvironment called ‘the niche'. In the bone marrow, HSCs receive signals from both the endosteal and vascular niches. The posterior signalling centre (PSC) of the larval Drosophila haematopoietic organ, the lymph gland, regulates blood cell differentiation under normal conditions and also plays a key role in controlling haematopoiesis under immune challenge. Here we report that the Drosophila vascular system also contributes to the lymph gland homoeostasis. Vascular cells produce Slit that activates Robo receptors in the PSC. Robo activation controls proliferation and clustering of PSC cells by regulating Myc, and small GTPase and DE-cadherin activity, respectively. These findings reveal that signals from the vascular system contribute to regulating the rate of blood cell differentiation via the regulation of PSC morphology.
Highlights
Self-renewal and differentiation of mammalian haematopoietic stem cells (HSCs) are controlled by a specialized microenvironment called ‘the niche’
Detectable levels if any of Robo 3 were present in posterior signalling centre (PSC) cells (Supplementary Fig. 1e–f)
Downregulating all three robos led to a decrease of Robo[1] and 2 in PSC cells (Supplementary Fig. 1a–f) and generated a stronger PSC defect (Fig. 1f–h) compared with reducing robo[2] alone (Fig. 1e–h), indicating that another Robo, probably Robo[1] could contribute to PSC morphology
Summary
Self-renewal and differentiation of mammalian haematopoietic stem cells (HSCs) are controlled by a specialized microenvironment called ‘the niche’. The posterior signalling centre (PSC) of the larval Drosophila haematopoietic organ, the lymph gland, regulates blood cell differentiation under normal conditions and plays a key role in controlling haematopoiesis under immune challenge. Robo activation controls proliferation and clustering of PSC cells by regulating Myc, and small GTPase and DE-cadherin activity, respectively These findings reveal that signals from the vascular system contribute to regulating the rate of blood cell differentiation via the regulation of PSC morphology. While not required for maintaining core progenitors[16], the PSC controlled the rate of haemocyte differentiation[17], most likely by regulating the maturation of intermediate progenitors, a heterogeneous cell population in the third instar larval LG7,15,18,19. On the basis of our data, we propose that inter-organ communication between the CT and the PSC is required to preserve the morphology and function of the PSC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
